Studies in organic synthesis

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The ultimate challenge of this century in total synthesis of complex natural products and related compounds is to be able to debunk the myth that such compounds are not economically viable targets in the pharmaceutical industry (S. Baran. J. Org. Chem. 2010, 75, 4657). Accordingly, we are currently exploring the generality of a powerful synthetic cycloaddition reaction for the rapid construction of natural and non-natural steroids and higher terpenoids. This novel anionic-based cycloaddition reaction discovered in our laboratory leads to polycyclic compounds in one or two-steps by combining two building blocks (mono or bicyclic) with complete control of chirality. Being highly convergent, this new synthetic strategy can be used for target-oriented synthesis of selected natural products to demonstrate its value and later on for diversity oriented synthesis for the discovery of new biological active compounds in industry. In order to demonstrate the potential of this novel strategy, we have recently reported the first total synthesis of Ouabain (Angew. Chem. Int. Ed. 2008, 47, 1272). This complex cardioactive steroid recently being identified as a human endogenous hormone has a direct link with hypertension. This novel chemical knowledge has led to the elaboration of research project on hypertension and on the study of the biosynthetic pathway of endogenous Ouabain. We have also completed the total synthesis of Hippuristanol, a steroid that could lead to develop novel-mechanism-based anticancer drugs. We are also working on the synthesis of the anticancer agent, Bruceantin, the neurotoxin Batrachotoxin, the anticancer agent Taxol and related analogues. We have also a renewed interest to investigate novel aspect of stereoelectronic effects in relation with conformation and reactivity of a large number of organic functional groups.